JP2004138619A - Method of detecting and compensating for undersupply of testing striate body - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of detecting undersupply of a test element to be analyzed and a method of compensating for undersupply thereof if needed, and to provide an analyzing apparatus and a test element suitable for detecting undersupply. <P>SOLUTION: The undersupply of the test element is surely detected and calculated if needed by irradiating the test element to be analyzed in the testing wavelength range. For that purpose, the element contains a test material which interacts with a radiation in the testing wavelength range depending on the contact with the amount of the sample supplied. <P>COPYRIGHT: (C)2004,JPO

Description

The present invention relates to a method for the detection of underdosing of analytical test elements and, where necessary, compensation for underdosing. Furthermore, the present invention relates to an analysis device and a test element which are suitable for detecting under metering.

In today's analytical methods, photometric evaluation of analytical test elements is one of the conventional methods for quickly identifying the concentration of an analyte in a sample (eg, US Pat. 4, Patent Document 5, Patent Document 6, and Patent Document 7). Generally, photometric evaluation is used in the field of analysis, environmental analysis, and especially in the field of medical diagnosis. In particular, a test element that is photometrically evaluated in the field of blood glucose diagnosis from capillary blood is very important.

一般 A general trend when conducting analytical tests is to reduce the sample volume. This is often explained by the very small sample volume. For example, in the field of blood glucose identification, a blood drop is collected from the diabetic patient's own finger pad abdomen. The reduction in blood volume required for the test can contribute to reducing the pain to the subject from blood sampling. This is especially because a small amount of required sample volume can select a slightly lower puncture for blood collection than if the required sample volume is large.

(4) The test element in which the original reaction between the analyte and the sample proceeds, and especially the reduction of the test area, leads to the reduction of the sample volume. However, since the size of the photometric test area plays an important role for reliable analyte concentration identification, any reduction in the calibration area for photometric evaluation test elements has proven impractical. Furthermore, it is important that the photometric inspection area of the assay area be wetted by the sample as completely and as homogeneously as possible. However, this is often not guaranteed from the very beginning with just a small sample volume. It is therefore important to identify whether the sample material is actually sufficiently present at each measurement and / or whether the sample material results in a flat homogeneous staining of the assay area.

In general, a photometer designed for the so-called "Home-Monitoring" consisting of a reflection photometer currently available on the market and a blood glucose test element ("test striatum") compatible with it. In blood glucose testing devices, the detection of possible underdosing of the test area of the test striatum can be visually detected by the user (eg, Glucotouch® from Lifescan Inc., Roche Diagnostics). "Accutrend" (Registered trademark) of Gesellschaft Mit-Bechlenktel-Haftung, in this case) or two or more closely adjacent or partially overlapping assay zones ("light Underscores in the test area of the test striatum, which can occur in any of the comparisons of the diffuse reflection values obtained by measuring the area Detection is carried out (see, for example, US Pat. No. 5,049,045 and the product “Glucotrend” ® from Roche Diagnostics Gesellschaft Mit Beschlenktel-Haftung).

In the case of visual inspection, it is necessary to determine whether the criteria for sufficient wetting of the verification area are met. In particular, in the case of visually impaired persons, undercorrected test striatum can cause measurement errors in some circumstances. When the required volume is small and thus the area is small, a visual inspection of the dispensed sample volume hits its limit even for a visually-impaired person.

Very reliable under metering detection can be achieved by means of a comparison of two or more adjacent or partially overlapping light spots. However, a detected underdispensing always results in the measurement device not outputting a measurement result with the underdispensed test element. Furthermore, two or more adjacent light spots cause an increase in the required sample volume as well as an increase in the area that must be covered with the sample liquid compared to the light spots.

US Pat. No. 5,077,059 proposes the detection and inspection of the wetting rate of the test area of the test element, the identification of an increase in transparency and a decrease in the diffuse reflection of the test area due to wetting by the sample liquid. To this end, the dry non-wetting assay area is first illuminated and diffuse reflection is detected by the device. Wetting of the test element causes the diffuse reflection or the measured diffuse reflection value to decrease until the diffuse reflection value reaches a plateau value at full wetting. When the plateau of the diffuse reflection is recorded by the inspection device, the sample supply to the test element is interrupted. After detection of the sample volume, the same optical system is used to measure the diffuse reflection value of the test element caused by the analyte-dependent dye formation. Upon completion of the reaction between the dye-forming reagent and the analyte, the analyte-dependent change in diffuse reflection also reaches a plateau value.

濃度 The analyte concentration is calculated using an analyte-dependent diffuse reflection value (plateau value), and the plateau value measured when the test element is completely wetted is also taken into consideration. Therefore, the calculation of the analyte concentration is performed in consideration of the supplied sample volume. When wetting is not complete, under- metering of the assay element is detected, allowing a range of reduced diffuse reflections to identify the actual amount of sample present.

Optical structures providing the same radiation source, radiation path and detector for each measurement are used for the measurement of the diffuse reflection change caused by the wetting of the calibration area of the test element and for the measurement of the analyte-dependent diffuse reflection change Is done. This consequently allows the identification of the concentration of the analyte only by a number of successive measurements, thereby allowing the identification of each plateau value.

Further, it is assumed that the apparatus is configured to be able to guarantee the interruption of the sample supply when the first plateau value is reached, for example.

Therefore, the measuring method and the structure of the apparatus have proven to be expensive and complicated.

Furthermore, Patent Document 7 discloses a method for detecting sufficient wetting of an analytical test element using an aqueous sample liquid. In addition to detecting possible under-dispensing, this method can likewise be used to evaluate the sample volume actually supplied to the test element. This method takes advantage of the optical absorption properties of water in the sample liquid, particularly in the infrared spectral region, thereby limiting its use to aqueous sample liquids. In addition, there is a need for IR optics whose structure has proven to be often expensive, based on the absorption band of moisture.

European Patent Application Publication No. 08199943 U.S. Pat. No. 6,036,919 German Patent No. 3130749 U.S. Pat. No. 5,846,837 International Publication No. 01/48461 pamphlet US Patent No. US5114350 WO 83/00931 pamphlet

The object of the present invention is to eliminate the disadvantages of the prior art. In particular, the invention is based on the task of providing a method and a device for detecting metering errors with high accuracy without the need for expensive optical systems or methods therefor.

This problem is solved by the objects of the invention as characterized in the independent claims. Advantageous embodiments of the invention are described in the dependent claims.

The object of the present invention is an analyzer for calculating a sample amount in an evaluation area of a test element. The analyzer includes an illumination unit that emits radiation in a test wavelength region where the test substance interacts with the irradiation depending on contact with a sample substrate. Further, the device includes a detector that detects radiation that interacts with the test substance, thereby producing a detection value.

(4) The sample amount can be identified in the evaluation area of the test area by using the evaluation device. For this purpose, the detected radiation is compared with a known detection value of the test substance at a known sample volume in the evaluation area and is taken into account for the calculation of the sample volume.

Further, a test element for detecting a sample amount is an object of the present invention. The test element interacts with the analyte of the sample, such that upon irradiation of the test area within the detection wavelength range, the analysis-specific reagent interacts with the radiation depending on the analyte concentration. Includes test area. In order to detect the amount of sample supplied to the test element, the test element further interacts with the sample substrate of the sample, whereby the test substance is supplied to the test area in the test wavelength range upon irradiation of the test area. Includes a test substance in the test area that interacts with the radiation depending on the sample volume.

With the aid of the device or the method according to the invention, it is possible to reliably detect metering errors on the test element. In this case, the actual amount of sample supplied or the coverage on the test element is preferably calculated, so that a correction calculation can be made in the event of a dispensing error and the user is not forced to supply a new blood supply. However, when the coverage is below a predetermined threshold, the measurement evaluation is interrupted in another advantageous embodiment, since the accuracy of the measurement cannot be guaranteed despite the correction calculation.

According to the invention, when the time course of the emission of luminescence is known after the irradiation of the sample on the test area, the measuring conditions can be predetermined correspondingly, whereby the luminescence intensity is supplied from The sample volume can be inferred. This can be achieved, for example, if the measurement time is always 4 seconds after the excitation of the test substance. From the emission intensity measured with a known sample amount, the sample amount can be inferred from the emission intensity measured there.

The inspection wavelength range can be freely selected by a suitable selection of the test substance, for example, there is no need to measure in the IR range. Thereby, the structure of the device optical system can be advantageously maintained in terms of cost. In addition, it is possible to avoid overlapping of water zones that interfere in the IR region.

The term "test substance" includes a substance that interacts with a sample substrate upon contact with the sample substrate. The contact between the sample substrate and the test substance is carried out in such a way that upon irradiation of the test substance in the test wavelength range, a detection value which varies depending on the sample amount is detected. For example, a change in the detected value is caused by a change in the physical and / or chemical properties of the test substance upon contact with the sample substrate.

Detected value is understood here as the value generated after irradiation of the test element, for example, by radiation reflected, transmitted or emitted from the test element.

When radiation is reflected or transmitted from the test element, the change in the detected value can be justified, for example, by a change in the absorption behavior of the test substance. In this case, it is conceivable, for example, that the test substance forms a dye that absorbs in the test wavelength region upon contact with the sample substrate. The detection value is generated by radiation reflected or transmitted from a test element that depends on the dye formed in that case. In addition, the test substance may contain, for example, a luminescent substance, whereby upon contact between the sample substrate and the test substance, the illuminant is excited by irradiation within the test wavelength range, and the intensity of the luminous substance may be identified by the amount of sample supplied. Conceivable.

The term “contact or interaction with the sample substrate” is understood in the sense of the present invention as any possible form of interaction between the sample substrate and the test substance. When the test substance is a color former, for example, a dye can be formed based on a chemical reaction or Van der Waals interaction. The absorption of the dye formed is then measured in the evaluation area of the test area, which is taken as a measure of the amount of sample supplied. When the test substance is a luminescent substance, all possible interactions with the sample substrate which also block and / or enable the luminescent substance are conceivable. In this case, it is possible, for example, to use a luminescent substance as test substance and to change its luminescence behavior upon contact with the sample substrate (for example, by rapid cooling of the luminophore). Similarly, a substance capable of emitting light upon contact with the sample substrate may be used first. As mentioned above, the term "contact with the sample substrate" includes, in particular, that the intensity of the luminophore is interrupted merely by collisions between the molecules of the test substance and the sample substrate molecules. Thus, the interaction of the test substance with radiation in the test wavelength range depends on contact with the sample substrate, either directly (for example, by the formation of a dye or luminescent substance) or indirectly (for example, by changing the intensity of the luminescent substance by a quenching step). Can be provided.

Basically, this method is used as long as the measurable change in the interaction of the test substance is caused by radiation upon contact with the sample substrate, and this measurable change allows a back inference to the supplied sample volume. It is not limited to a specific interaction between the sample substrate and the test substance, nor is it limited to a process that affects the interaction between the electromagnetic radiation and the test substance depending on the sample volume.

The term "sample amount" can be understood in the sense of the present invention as, for example, an indication of the absolute volume or amount of a supplied sample. However, often the absolute sample volume is not identified, but preferably is identified by the coverage of the test area which infers a sufficient sample supply. In general, there are many possibilities for inferring the amount of sample that interacts with the analyte-specific reagent as a sample volume criterion. The prior art describes an analyte identification method that infers the amount of sample that comes into contact with an analyte-specific reagent based on, for example, the coverage of the test area. For example, such a method and apparatus is disclosed in US Pat.

Based on the precise identification of the sample volume on the test element, the method or device according to the invention is preferably used for the identification of the analyte concentration. In this case, the invention has proven to be particularly suitable in the context of modern analytical methods, in particular in the field of home monitoring. In this application field, it is an important endeavor to identify the analyte concentration accurately despite the reduction of the sample size without specifying expensive conditions in terms of equipment, so special Are imposed. However, undoubtedly special home monitoring devices are often operated by unskilled and elderly users, often resulting in incorrect metering of the sample to the test element. The device according to the invention allows for a simple instrument structure, which reduces the production costs required for the analyzer and allows the patient to afford as a home monitoring device. With the device / method according to the invention, the amount of sample required for the analysis can be reduced, thus eliminating the burden of blood sampling on the patient. In this case, it is taken into account that the dosing error becomes serious, since in the identification of the concentration from just a small amount of sample already a small variation in the amount of the sample can lead to a considerable error in the concentration test.

This type of metering error is detected by the preferred embodiment of the device according to the invention, as described above, by comparing the detected radiation with the known detection value of the test substance of a known sample volume in the evaluation area. In this case, the comparison with the known detection value can advantageously be made by simply recording the excess or the decrease of the known absorption value without a detailed quantification of the sample volume.

In the solution according to the invention, however, it is possible not only to reliably detect an under metering of the evaluation area of the test element, but also to compensate (preferably to a certain threshold). Therefore, the user is not required to take a new blood sample in the case of a dispense error.

過 Underdosing in the sense of the present invention occurs when the test area (evaluation area) on the surface of the test element is not completely covered with the sample liquid. Thus, for example, the area evaluated by diffuse reflectance photometry is not entirely provided to the analyte assay reaction, but only a portion thereof is provided. The absorption of the analyte assay reaction is then related to an incorrectly large sample volume, whereby too low a concentration is output as a measurement. The device according to the invention corrects the measured values in view of the actually output sample volume.

The term “evaluation area” includes the area of the test area which is illuminated by the lighting unit in this case, and may for example be equal to the test area, so that a complete illumination of the test area takes place.

検 出 In addition to the detection and compensation of the actual under-distribution, the inhomogeneity which is not reduced to too little sample liquid by the sample distribution in the assay element is also taken into account. Such inhomogeneities in the test element are, for example, production-limited.

In the context of the present invention, the term “sample” is understood in particular as a body fluid such as blood, saliva, urine or a liquid derived from a body fluid such as serum, plasma, diluted blood-, saliva- or urine sample. .

The identification of an analyte from a sample is sufficient in the prior art, for example using a test element, as is known from US Pat. Done. The analyte then preferably reacts with the reagents present in the test element and forms a dye depending on the analyte concentration. The analyte concentration is calculated based on the measured absorption of the dye. The absorption is measured, for example, by reflection photometry, but transmission or fluorescence can also be measured. In general, the device / method according to the invention is not limited to diffuse reflectance measurements, but also encompasses other variants.

In a preferred embodiment, the diffuse reflection transport provided for the measurement of the analyte is chosen as large as possible. This means that the interval between the minimum and maximum diffuse concentrations of the analyte concentration is maximal, since the diffuse reflection transport greatly affects the accuracy of the reflection photometric measurement. The diffuse reflection transport is in this case proportional to the area covered by the sample liquid of the assay element. When a color former is used as the test substance, cover it so that as little diffuse reflection as possible, preferably zero diffuse reflection, is observed when the evaluation area inspected at the selected wavelength (inspection wavelength area) is completely wetted. It has been found to be preferable to choose the color of the chromophore formed as a function of the rate, whereby a precise identification of the area of the test element actually wetted with a large difference in the diffuse reflection values is achieved. Particularly advantageously, the highest possible diffuse reflection should be obtained in the absence of the sample.

In practice, it is desirable to determine the lower threshold of the area of the test element covered with the sample solution. In a preferred embodiment, the calculated sample volume value is compared to such a pre-stored threshold. Since the accuracy of measurement corresponds to the quality requirement of the measurement system up to this threshold, the output of measured values for values below this threshold should be suppressed.

The relationship between the diffuse reflection found and the actually wetted area is stored in a measuring device in a manner known per se or together with other loading-specific data of the test element used in the measuring device, for example, in a bar chart. The code can be delivered using a ROM key or via an input keyboard.

In the sense of the present invention, for example, fluorescein can be used as test substance.

接触 Upon contact with the sample substrate, fluorescein is hydrolyzed by the water contained in the sample substrate. Fluorescein is subsequently excited for luminescence, and an increased luminescence intensity dependent on the wetting of the test area appears.

Furthermore, as test substance in the sense of the present invention, a color former may be used which indicates the presence of a sample in the test element by means of an easily observable color change. Many substances are known that change their color based on the presence of a sample. In this case, for the present invention, how the sample interacts with the substance capable of color change is of only secondary importance. In this case, it is important that the magnitude of the color change has a correlation with the sample amount or the coverage in the evaluation area. Therefore, preferably, the amount of the sample interacting with the reagent can be inferred from the amount of the sample in contact with the test substance.

When the sample is not supplied to the test area, the test substance, preferably in the test wavelength range, does not interact with the radiation. After supplying the sample, the test substance more preferably does not interact within the detection wavelength range. When a chromophore is used as the test substance, the test wavelength range is preferably between 500 and 600 nm, advantageously at 572 nm.

試 料 Sample substrate in the sense of the present invention is not called an analyte, but is understood as all sample components present in a sample in a sufficient amount. For example, the term "sample substrate for a biological fluid" may contain water, such that the water contained in the sample substrate forms a dye in the test area containing the color former.

Here, a color change means that a chemical bond changes its color (color change) in the presence of a sample solution, and shifts from colorless to a colored state (color generation), or conversely, changes from a colored state to a colorless state (color change). Extinction).

(4) Preferably, the chemical bond shifts from a colored state to a colorless state in the presence of the sample solution. In the ideal case, the diffuse reflection measured here at the wavelength of the chromophore so generated is inversely proportional to the area of the test element of the test striatum actually wetted by the sample solution.

In this case, for example, a test element formed from two layers is used. This stratification ensures that the detected sample volume or coverage of the test area allows a back inference to the sample volume in contact with the analyte-specific reagent. For example, multilayer test elements are described in US Pat. The analyte-specific reagent is, for example, 2-phosphorous-18-molybdic acid (P ₂ Mo ₁₈ O _x ), and is used for identifying the glucose concentration.

グ ル コ ー ス Glucose present in the sample reacts with the reagent under the formation of a dye. Using an analyzer, the analyte-dependent dye absorption is first measured in the first wavelength region 660 nm in the example of 2-phospho-18-molybdic acid, whereby the glucose concentration can be identified. Subsequent or before the detection of the analyte-dependent dye, a measurement is made in the test wavelength range, for example, the absorption of the analyte-dependent dye is detected. In an advantageous embodiment of the test element for sample volume identification, the test area contains chlorophenol red as an analyte-dependent color former. After a sample, for example, blood is applied to the test area, the sulfonic acid group of chlorophenol red is opened by water contained in whole blood, and a dye having an absorption maximum value of 572 nm is formed.

After detecting the absorption of chlorophenol red at で 572 nm, the measured absorption value is compared with the absorption value of chlorophenol red at a given known sample volume. By comparing the absorption values of the chlorophenol reds, the sample volume of the blood sample can be inferred. The calculated sample volume is subsequently taken into account in the glucose identification and the calculated glucose concentration is accurately calculated in view of the applied sample volume. Therefore, a preferred analyzer therefor comprises an illumination unit capable of emitting radiation in at least two wavelength ranges.

Therefore, the measurement for identifying the sample amount is preferably performed in a wavelength region different from the analytical identification. This allows maximum diffuse reflection transfer, especially for sample volume and analytical identification, as a result of which the accuracy of the method is optimized.

Furthermore, an object of the present invention is a method for calculating a sample amount in an evaluation area of a test element.

方法 This method involves irradiating the sample to the test area of the test element. Here, the test area is illuminated in such a way that at least one evaluation area of the test area is detected by radiation within the inspection wavelength range. The test area of the test element contains a test substance that interacts with the sample substrate of the sample in such a way that the test substance interacts with electromagnetic radiation in the test wavelength range depending on contact with the sample substrate. Detection of radiation interacting with the test substance is performed, thereby generating a detection value. By comparing the known detected value of the test substance with the detected radiation with the known sample amount in the evaluation area, the sample amount in the evaluation area is calculated.

好 ま し い A preferred embodiment of the method occurs as described above. The advantageous embodiments of the device and the test element are suitable for carrying out this method.

The invention is explained in more detail by means of the figures and the following examples.

In the following, for the sake of simplicity and clarity, when a color developing agent is used as the test substance, the chemical bond used as an indicator of the presence of the sample liquid in the evaluation area and the standard used as a reference changes from a colorless state without sample contact to a colored sample Describe the always advantageous case of transition to the state. Of course, the invention is not limited to the case. With similar considerations, the present invention can be diverted without difficulty to the case of "color change" and "color loss". These cases should be explicitly included.

分析 The analyzer 1 shown in FIG. 1 includes a test element 2 and an evaluation device 3. The test element 2 is formed by a supporting foil 5 made of synthetic resin elongated as the test striated body 4 and a test area 7 fixed to the upper flat side 6 of the supporting foil 5.

The test element 2 is inserted into the housing 11 of the evaluation device 3 through the opening 10 into the test element holder (not shown) and positioned at the measurement position. Evaluation device 3 includes measurement and evaluation electronics 13 implemented by circuit board 14 and integrated circuit 15. An optical transmitter, preferably implemented as a light emitting diode (LED), connected to the measurement and evaluation electronics 13, and a detector, preferably implemented as a photodiode, which is a component (not shown) of the optical measuring device.

FIG. 2 shows in detail the application of the method according to the invention in an analyzer with a photoconductive test element as described, for example, in US Pat. In this case, the application of the method and the device according to the invention has proven to be particularly preferred, since the prior art customary methods for detecting under metering in such devices are often not applicable.

(4) In order to perform the analysis, a droplet of the sample liquid 21 is applied to the side (upper side) of the test area 7 separated from the support foil 5. The application of the sample is such that only the first subsection 22 of the test element 2 positioned at the measuring position is in the housing 11, while the second subsection 23 including the test area 7 protrudes from the housing 11, so that it is easily accessible What you can do is easier. The liquid penetrates under dissolution of the reagent contained in the test area 7.

反 応 The reaction between the reagent system and the analyte contained in the sample causes an optically measurable change, especially a color change. For the photometric evaluation, the intensity of the secondary light diffusely reflected by the primary light of the first wavelength when the evaluation area 24 of the test area 7 is irradiated is measured. This takes place by means of a special design of the test strip 2 and of the part of the optical measuring device 18 which works with it in the illustrated light-conductive test element.

The support foil 5 includes at least one optical system light guide layer 26. Detailed information on photoconductive elements whose light transport is based on total reflection can be read from the relevant literature.

に お い て In the example shown, the test striatum 2 is used for the identification of the glucose concentration and therefore contains the reagent 2-phosphor-18-molybdic acid in the test area. This reagent reacts with glucose to form a colored complex that absorbs at about 660 nm. Reagents used in test carriers for the assay of glucose concentration are well known in the prior art and are described, in particular, in US Pat. In principle, any other form of reagent system, preferably in which the detection wavelength is distinguished from the test wavelength range, is of course conceivable. Further, there is a possibility that the analyte to be identified within the detection wavelength region is directly detected without the detection wavelength region interacting with the reagent in advance.

Test element 2 also contains a color former present in test area 7. The color former reacts with the dye chlorophenol red after the sample supply 21 due to the moisture present in the sample.

When the test striatum 2 is evaluated here by the analyzer 1, radiation is first emitted in the detection wavelength range 660 nm, and the radiation reflected from the test area 7 is detected depending on the glucose concentration present in the sample. Is done. The detected signal intensity first corresponds to the absolute glucose amount present in the measured sample. Subsequently, the test area is illuminated with an inspection wavelength range of about 572 nm. As soon as the chlorophenol red is absorbed in the presence of moisture in this wavelength range and the test area 7 is completely covered by the sample 21, almost no diffuse reflection is immediately detected.

In the above example, since the sample 21 is a blood drop, it may be assumed that there is sufficient moisture in the sample, and when the coloring agent comes into contact with the sample, the coloring agent is completely replaced immediately. Basically, one can think of the various contents of the sample substrate that interact with the color former and form a dye. In this case it is merely to be noted that the interactor of the sample substrate is present in a sufficient amount, so that as soon as the test area comes into contact with the sample, the absorption of a given dye depends on the sample volume.

Unlike the prior art, for example, in which moisture is directly detected, the use of the test substance according to the invention allows the wavelength range of the test to be freely selected and provides a discontinuous absorption band. This makes it possible, for example, to avoid disturbing absorption bands of pure water in which overlapping can occur, by a suitable choice of the wavelength range.

(4) The detection signal of the dye in the inspection wavelength region is recorded and compared with, for example, the absorption value (calibration value) of the dye when the test region is completely covered by the sample. By comparing the calibration value with the measured absorption value, the volume of the sample can be calculated and calculated directly. Subsequently, the pre-calculated amount of glucose is related to the sample amount, which results in an accurate identification of the glucose concentration. This is notified to the user via the display 20. If the sample is under-dispensed within a range in which the measurement quality cannot be further guaranteed, the supplied sample amount falls below the stored threshold. If the fall below the threshold is determined by the device, the output of the measurement result is rejected and the user is informed of the invalid measurement on the display and is required to repeat the measurement.

FIG. 3 shows various absorption bands 30 and 34 of chlorophenol red detected in the test area when measuring various sizes of sample volumes. In the illustration of FIG. 3, the wavelength region nm is recorded when the test element does not absorb the diffuse reflection starting from 100% diffuse reflection and the sample is not supplied to the test element.

The maximum absorption value 31 of chlorophenol red is 572 nm as described above. When sufficient sample has been supplied to the test element and the test area is completely covered, the dye absorbs light and is recorded by the detector with a minimum diffuse reflection of light in the range of 9-13%. When diffuse reflection is measured in this range and near perfect light absorption occurs, sufficient sample has been supplied to the test element. However, when the light intensity exceeds a predetermined diffuse reflection value (for example, 15%), the sample is not sufficiently supplied to the test striatum, and the test striatum is under-metered. However, depending on the analyzer, it is possible to change from that value the diffuse reflection value at which the test element is regarded as underdosing. Preferably, for example, an underdosing of the test element is already recorded with 3% diffuse reflection. Based on the measured diffuse reflections, the amount of sample supplied or the coverage of the test area must be inferred before the glucose concentration can first be calculated. With the detected values recording the complete coverage of the test area, the measured diffuse reflectance values can be used to infer the coverage of the test area.

線形 A linear relationship appears between the diffuse reflection measured here and the coverage of the test area or the supplied sample volume.

In the second measurement in the region (32) at 650 nm and 900 nm, the absorption of the analyte-specific reagent is measured here. Light is absorbed at various intensities, depending on the absolute amount of glucose contained in the sample. FIG. 3 specifically shows an increase in diffuse reflection when the absolute glucose amount decreases. The reduction in absolute glucose amount is achieved at the same glucose concentration in each sample by reducing the sample volume in the example shown, and thus by insufficient coverage of the test area.

When, for example, diffuse reflectance is measured at 750 nm for glucose concentration identification, a sufficient sample volume of 75% diffuse reflectance value infers glucose concentration. However, measurement of the same sample in an under-weighed test area would erroneously infer a glucose concentration that was too low, since diffuse reflection occurs between 85% and 90% diffuse reflection. Thus, the glucose concentration must be identified taking into account the measured absolute glucose amount and the calculated coverage of the test area.

However, when the light intensity exceeds the threshold 35 in the test wavelength region, it is proved that the identification of the glucose concentration is unreliable and insufficiently accurate by the calculated covering ratio despite the correction of the glucose measurement value. Will be done. Such under-dispensing occurs, for example, when less than one third of the test area is covered. The glucose concentration is not further indicated to the user when the corresponding diffuse reflection value is exceeded, instead the user is required to repeatedly supply the sample.

FIG. 4 illustrates a method according to the invention of under-metering detection, which is performed analogously based on the detection of luminescence. An advantageous embodiment arises as described above, in which again a correction of the measurement value must be performed when the threshold value is exceeded / decreased, or a threshold value whose output of the measurement value is rejected can be identified. For example, such a method based on luminescence measurements is used for the identification of glucose in blood.

In the example shown, a test area of a test element containing Fluorosphor, fluorescein is prepared as a test substance. As analyte-specific reagents for glucose assays, the test area contains the substance NAD ⁺ . By supplying a blood sample to the test area, the luminophore reacts with the water contained in the sample and fluorescein is hydrolyzed as a test substance.

FIG. 4 shows the time course of the emission intensity after application of the blood sample to the test area and after irradiation of the test area with the excitation wavelength. After contact with the sample substrate, the emission intensity of fluorescein due to hydrolysis changes. When the test area is illuminated at 485 nm, excitation of exclusively hydrolysed fluorescein occurs, which emits emission radiation in the range> 570 nm after about 1 second from the test area. Preferably, the emission intensity is measured about 4 seconds after irradiation of the test area. It is clear that the intensity of the emitted radiation depends on the amount of sample supplied, since only a part of the test substance in contact with the sample substrate is excited. When too little sample is supplied to the test area, fluorescein is not completely hydrolyzed, resulting in reduced luminescence intensity. There is a linear transition between the wetting of the test area by the sample and the emission intensity. When the supplied sample quantities are not so distinguished, as shown in curve transitions 1 and 2 in FIG. 4, there is a corresponding slight difference in the emission intensity. When the supplied sample volume is further reduced (see curve progressions 3 and 4), this causes a corresponding reduction in the emission intensity.

An analyzer including a test element. 2 is an analyzer including a photoconductive test element. It is a graph which shows the absorption band of chlorophenol red in a wavelength region from 550 nm to 950 nm. It is a graph which shows the luminescence measurement result by fluorescein 420nm.

Explanation of reference numerals

REFERENCE SIGNS LIST 1 analysis device 2 test element 3 evaluation device 4 test strip 5 support foil 6 upper flat side 7 test area 10 opening 11 housing 13 evaluation electronic device 14 circuit board 15 integrated circuit 18 optical measurement device 20 display 21 sample liquid 22 1 partial section 23 second partial section 24 evaluation area 26 optical system light guide layer 30, 34 absorption band 31 absorption maximum value

Claims (18)

A method for calculating a sample amount in an evaluation area of a test element,
Irradiating said sample within an inspection wavelength region in which a sample is provided to a test area of a test element, wherein at least one evaluation area of the test area is detected by radiation;
The test area comprising a test substance that interacts with the sample substrate of the sample in such a manner that in the irradiation the test substance interacts with electromagnetic radiation in the test wavelength range depending on contact with the sample substrate;
Detecting the radiation, wherein the radiation interacts with the test substance, thereby producing a detection value;
Calculating a test amount in the evaluation area by comparing a known detection value of the test substance with the detected radiation in a known sample amount in the evaluation area. The method according to claim 1, wherein the determination of the sample amount is performed by comparing the detected radiation with the threshold value in order to check whether the sample amount in the evaluation area is below or above the threshold value. The method of claim 1 wherein the test substance does not essentially interact with radiation within the test wavelength range when the sample does not cover the evaluation area. Used for the analysis of the analyte in the sample, the analyte-specific reagent interacts with the analyte in this way in the test area, thereby detecting the analyte in the detection wavelength range in a concentration-dependent manner The method of claim 1, wherein the value is detected. 5. The method according to claim 4, wherein the amount of the sample interacting with the reagent is inferred from the amount of the sample in contact with the test substance. The method according to claim 4, wherein the concentration of the analyte is calculated in consideration of the detected sample amount. 5. The method according to claim 4, wherein the test substance does not essentially interact with the radiation in the detection wavelength range. An analyzer for calculating a sample amount in an evaluation area of a test element,
An illumination unit that emits radiation in the test wavelength range in which the test substance interacts with the radiation depending on contact with the sample substrate;
A detector for the detection of said radiation, wherein the radiation interacts with the test substance, whereby a detection value is generated;
An analysis apparatus comprising: an evaluation unit for calculating a sample amount in an evaluation region of a test region by comparing a known detection value of a test substance with detected radiation with a known sample amount in the evaluation region. 9. The analyzer according to claim 8, comprising an illumination unit that emits radiation in at least two wavelength ranges. The analyzer according to claim 8, wherein the wavelength region is in a range of 500 nm to 1000 nm or in a range of 360 nm to 500 nm. The analyzer according to claim 8, which is used for identifying a glucose concentration. A test element for detecting a sample amount,
An analyte-specific reagent that interacts with the analyte of the sample, whereby the reagent interacts with the radiation upon irradiation of the test area within the detection wavelength range depending on the analyte concentration; Contains a test area containing a specific reagent,
The test substance interacts with the sample substrate of the sample, thereby causing the test substance to interact with the radiation in the test wavelength range upon irradiation of the test area, depending on the amount of sample supplied to the test area. A test element containing the test substance. The test element according to claim 12, wherein the test substance in the test element is a luminescent substance. 13. The test element according to claim 12, wherein the test substance is a coloring agent. 15. The test element according to claim 14, wherein upon contact with the sample substrate, the sample forms essentially completely absorbing dye in the test wavelength range as soon as the sample has essentially completely covered the evaluation area. 13. The test element according to claim 12, wherein the test substance reacts with moisture contained in the sample substrate. An analyzer according to claim 11, comprising the test element according to claim 12, 13, 14, 15, or 16. A method according to claim 1, wherein the method is carried out using the analyzer according to claim 8, 9, 10, 11 or 17.

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